Chihara Dai, Steiner Raphael E, Nair Ranjit, Feng Lei, Ahmed Sairah, Strati Paolo, Malpica Luis, Griffith Donna P, Mathew Shivon A, Montinez Wirt, Masand Gita, Samaniego Felipe, Rodriguez Maria A, Hagemeister Fredrick B, Fayad Luis E, Iyer Swaminathan P, Nastoupil Loretta J, Neelapu Sattva S, Flowers Christopher R, Westin Jason R
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX.
Blood Adv. 2025 Apr 8;9(7):1485-1491. doi: 10.1182/bloodadvances.2024014635.
Treatment options are limited for both relapsed/refractory primary and secondary central nervous system (CNS) lymphoma and the prognosis remains poor. Previous studies have shown the activity of Bruton tyrosine kinase inhibitors and programmed death-1-targeted therapies in CNS lymphoma, and studies suggested potential synergy. Therefore, we conducted a phase 2 trial that combined ibrutinib with nivolumab for patients with relapsed/refractory CNS lymphoma. Patients received 560 mg oral ibrutinib daily with 240 mg IV nivolumab every 14 days (28 days per cycle). Patients who had partial or complete response after 6 cycles of treatment could continue therapy for up to 2 years unless progression or unacceptable toxicity occurred. A total of 18 patients were enrolled with a median age of 63 years (range, 43-88). The median number of previous lines of therapy was 2 (range, 1-4); 55% had refractory disease, 17% previously underwent stem cell transplant, and 11% previously underwent chimeric antigen receptor T-cell therapy. The best overall response rate was 78% and the best complete response rate was 50% (95% confidence interval, 26-74). The median progression-free survival and overall survival was 6.5 months and 21.0 months, respectively, and 3 patients continued to be in remission for >2 years. Treatment was generally well tolerated but 2 patients stopped treatment because of fatigue. Ibrutinib and nivolumab had reasonable safety and clinical activity in patients with refractory/relapsed CNS lymphoma and warrants further investigation. This trial was registered at www.ClinicalTrials.gov as #NCT03770416.
复发/难治性原发性和继发性中枢神经系统（CNS）淋巴瘤的治疗选择有限，预后仍然很差。先前的研究表明布鲁顿酪氨酸激酶抑制剂和程序性死亡-1靶向疗法在中枢神经系统淋巴瘤中的活性，并且研究提示了潜在的协同作用。因此，我们开展了一项2期试验，将伊布替尼与纳武单抗联合用于复发/难治性中枢神经系统淋巴瘤患者。患者每日口服560mg伊布替尼，每14天静脉注射240mg纳武单抗（每周期28天）。在6个周期治疗后出现部分或完全缓解的患者可以继续治疗长达2年，除非出现疾病进展或不可接受的毒性。共有18例患者入组，中位年龄为63岁（范围43-88岁）。既往治疗的中位线数为2（范围1-4）；55%患有难治性疾病，17%既往接受过干细胞移植，11%既往接受过嵌合抗原受体T细胞疗法。最佳总缓解率为78%，最佳完全缓解率为50%（95%置信区间，26-74）。中位无进展生存期和总生存期分别为6.5个月和21.0个月，3例患者持续缓解>2年。治疗总体耐受性良好，但2例患者因疲劳停止治疗。伊布替尼和纳武单抗在难治性/复发性中枢神经系统淋巴瘤患者中具有合理的安全性和临床活性，值得进一步研究。该试验已在www.ClinicalTrials.gov注册，编号为#NCT03770416。
